Fenofibrate Treatment in SCI
Study Details
Study Description
Brief Summary
Cardiovascular disease-related morbidity in persons with spinal cord injury (SCI) occurs earlier in life, at a greater prevalence than that of the general population, and is the primary cause of death after the first year of injury. During the chronic phase of SCI, a characteristic dyslipidemia emerges, which is characterized by low serum high density lipoprotein cholesterol (HDL-C) concentrations, with values often qualifying to be an independent risk factor for coronary artery disease, and elevations in serum triglycerides (TG). Serum low density lipoprotein cholesterol concentrations in those with SCI are usually similar to those of the general population. The current proposal in persons with SCI aims to determine the safety and efficacy of short-term fenofibrate treatment, an anti-lipid medication whose primary action lowers serum TG and raises serum HDL-C levels.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
Although considered a modifiable risk factor for coronary artery disease (CAD) in the general population, the magnitude of physical activity required to promote cardiorespiratory fitness and a clinically meaningful change in blood-derived biomarkers of CAD is not achievable in those with a severe physical disability, such as with immobilizing paralysis from spinal cord injury (SCI). During the chronic phase of SCI, a characteristic dyslipidemia emerges, with mean serum high density lipoprotein cholesterol (HDL-C) concentrations <40 mg/dl, a threshold level for HDL-C that is appreciated to be an independent risk factor for CAD, elevations in triglycerides (TG) to concentrations at, or near, target values for the general population that trigger clinical intervention, and low density lipoprotein cholesterol (LDL-C) concentrations that are within the normal range. It should not be a surprise that cardiovascular disease (CVD)-related morbidity in persons with SCI occurs earlier in life, at a greater prevalence than that of the general population, and is the primary cause of death after the first year of injury. Population-based epidemiological studies are unavailable for clinical guidance because of the relatively low incidence rates for SCI. Clinical target values used to initiate treatment in the general population may be inappropriate in those with SCI because of their unique pathophysiology. In the absence of significant physical activity and lifestyle modifications, it would seem that appropriate pharmaceutical options are needed to properly manage markers of CVD-related risk in persons with SCI. To date, there is limited empirical evidence to support the use of lipid-lowering treatments in persons with SCI.
Fenofibrate is a fibric acid derivate that activates peroxisome proliferator-activated receptor and lipoprotein lipase, leading to enhanced elimination of TG from plasma. In clinical trials where fenofibrate was used as a monotherapy, serum TG concentrations fell 41-53%, very low density lipoprotein (VLDL) fell 38-52%, LDL-C decreased 6-20%, and HDL-C improved by as much as 20%. In consideration for the nature of dyslipidemia in persons with SCI, fenofibrate appears to be an appropriate first-line agent for treatment in this cohort, especially because most of those with SCI have LDL values that are within the clinically acceptable range. In the general population, standard clinical practice for lipid-lowering treatment with fenofibrate monotherapy follows a known and clinically accepted timeline to monitor safety and to determine therapeutic efficacy. It is recommended that, if after 2 months of continuous therapy there are no beneficial changes to the lipoprotein profile, that treatment be discontinued (i.e., non-responders). Similarly, several large clinical trials have demonstrated that the peak therapeutic effects of fenofibrate are observed after 12-16 weeks of treatment (i.e., responders). The proposed study will test the efficacy of administering fenofibrate to persons with SCI, a severely immobilized cohort that does not have established clinical practice guidelines to treat dyslipidemia and appears to have unique considerations that may be hypothesized to call for a more disease-specific approach for care. If successful, the treatment will reduce clinical markers of CVD-related risk by modifying the concentration and number of particles that are known to contribute to incident cardiac events and mortality. It is anticipated that the insight gained from this investigation will provide clinicians with a proof-of-concept for instituting appropriate use of lipid lowering agents to treat the dyslipidemia that has been well described in persons with SCI.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Fenofibrate Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months |
Drug: Fenofibrate
Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood.
|
Other: No Intervention Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months |
Other: No intervention
A cohort of participants will be randomized to receive no study drug, but will engage in study encounters.
|
Outcome Measures
Primary Outcome Measures
- Triglyceride Concentration (Percent Change From Baseline) [two months from initiating drug treatment]
To determine the efficacy of fenofibrate monotherapy after 2 months of treatment to improve the lipoprotein profile; a successful response will be defined as a 25% reduction in the serum TG concentration at 2 months.
Secondary Outcome Measures
- Triglyceride Concentration (Percent Change From Baseline) [four months from initiating drug treatment]
To determine the efficacy of fenofibrate monotherapy to lower TG concentration at 4 months of treatment, when the peak therapeutic efficacy to drug treatment has been reported to occur.
Other Outcome Measures
- Adverse Event Profile [4 months]
Documentation and description of adverse events will be obtained in subjects who have received drug treatment compared to events occurring in the control group.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female, age 21 to 69;
-
Chronic (e.g., duration of injury at least 6 months), stable SCI (regardless of level of neurological lesion);
-
American Spinal Injury Association Impairment Scale (AIS) designation of A, B or C; and
-
TG concentration 135 mg/dl (paraplegia) or 115 mg/dl (tetraplegia).
Exclusion Criteria:
-
Acute illness or infection;
-
Reduced kidney function (by glomerular filtration rate (GFR <60 ml/min) or liver function tests (LFTs 2.5 standard deviations above the upper limit of normal);
-
Current pharmacological treatment with: HMG-CoA reductase inhibitors (statins), or any other hypolipidemic agent; anti-coagulant therapy; cyclosporine; or any other medications known to effect the TG concentration (i.e., -blockers, thiazides or estrogen);
-
Hypersensitivity to fenofibrate;
-
Existing diagnosis of atherosclerosis, congestive heart failure, or recent history of myocardial infarction (i.e., 12 months);
-
Pregnancy or women who may become pregnant during the course of the study, or those who are nursing;
-
Diminished mental capacity; and
-
Inability or unwillingness of subject to provide informed consent.
-
Existing diagnosis of diabetes mellitus, or the results from screening blood tests indicate that diabetes mellitus is present (and perhaps undiagnosed); laboratory thresholds for exclusion will be as follows: HbA1C 6.5% and fasting plasma glucose is
126 mg/dl.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Kessler Institute for Rehabilitation | West Orange | New Jersey | United States | 07052 |
2 | James J. Peters VA Medical Center, Bronx, NY | Bronx | New York | United States | 10468 |
Sponsors and Collaborators
- VA Office of Research and Development
Investigators
- Principal Investigator: Michael F LaFountaine, EdD, James J. Peters Veterans Affairs Medical Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- B1925-P
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Fenofibrate | No Intervention |
---|---|---|
Arm/Group Description | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months Fenofibrate: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood. | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months No intervention: A cohort of participants will be randomized to receive no study drug, but will engage in study encounters. |
Period Title: Overall Study | ||
STARTED | 15 | 8 |
COMPLETED | 10 | 6 |
NOT COMPLETED | 5 | 2 |
Baseline Characteristics
Arm/Group Title | Fenofibrate | No Intervention | Total |
---|---|---|---|
Arm/Group Description | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months Fenofibrate: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood. | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months No intervention: A cohort of participants will be randomized to receive no study drug, but will engage in study encounters. | Total of all reporting groups |
Overall Participants | 10 | 8 | 18 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
10
100%
|
8
100%
|
18
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
49
(14)
|
44
(13)
|
46
(14)
|
Sex: Female, Male (Count of Participants) | |||
Female |
1
10%
|
0
0%
|
1
5.6%
|
Male |
9
90%
|
8
100%
|
17
94.4%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
2
20%
|
0
0%
|
2
11.1%
|
White |
8
80%
|
8
100%
|
16
88.9%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Triglyceride Concentration (Percent Change From Baseline) |
---|---|
Description | To determine the efficacy of fenofibrate monotherapy after 2 months of treatment to improve the lipoprotein profile; a successful response will be defined as a 25% reduction in the serum TG concentration at 2 months. |
Time Frame | two months from initiating drug treatment |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Fenofibrate | No Intervention |
---|---|---|
Arm/Group Description | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months Fenofibrate: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood. | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months No intervention: A cohort of participants will be randomized to receive no study drug, but will engage in study encounters. |
Measure Participants | 10 | 8 |
Mean (Standard Deviation) [percent change from baseline] |
-40
(12)
|
-2
(16)
|
Title | Triglyceride Concentration (Percent Change From Baseline) |
---|---|
Description | To determine the efficacy of fenofibrate monotherapy to lower TG concentration at 4 months of treatment, when the peak therapeutic efficacy to drug treatment has been reported to occur. |
Time Frame | four months from initiating drug treatment |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Fenofibrate | No Intervention |
---|---|---|
Arm/Group Description | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months Fenofibrate: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood. | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months No intervention: A cohort of participants will be randomized to receive no study drug, but will engage in study encounters. |
Measure Participants | 10 | 8 |
Mean (Standard Deviation) [percent change from baseline] |
-40
(20)
|
7
(14)
|
Title | Adverse Event Profile |
---|---|
Description | Documentation and description of adverse events will be obtained in subjects who have received drug treatment compared to events occurring in the control group. |
Time Frame | 4 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Fenofibrate | No Intervention |
---|---|---|
Arm/Group Description | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months Fenofibrate: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood. | Subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months No intervention: A cohort of participants will be randomized to receive no study drug, but will engage in study encounters. |
Measure Participants | 15 | 8 |
Elevated liver enzymes |
2
20%
|
0
0%
|
Gastrointestinal discomfort |
2
20%
|
0
0%
|
Adverse Events
Time Frame | All blood sample results were reviewed by the study physician for the presence of adverse findings at each monthly visit during the 4 months of the treatment trial. | |||
---|---|---|---|---|
Adverse Event Reporting Description | The presence of an adverse finding in liver function tests, kidney function, CBC w/diff, or a change in the patient self-report health status were submitted to the Institutional Review Board (IRB) as an adverse event; the nature/severity of the event may have resulted in discontinuation of the subject from the study drug and continued participation in the trial, which was contingent upon the judgement of the study physician and the advice of the IRB. | |||
Arm/Group Title | Fenofibrate | No Intervention | ||
Arm/Group Description | Twenty subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive once daily fenofibrate therapy (i.e., 145 mg) for 4 months Fenofibrate: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood. | Ten subjects with adverse TG concentrations (i.e., paraplegia: >/=135 mg/dl; tetraplegia >/=115 mg/dl) will be randomized to receive no therapy for 4 months No intervention: A cohort of participants will be randomized to receive no study drug, but will engage in study encounters. | ||
All Cause Mortality |
||||
Fenofibrate | No Intervention | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/15 (0%) | 0/8 (0%) | ||
Serious Adverse Events |
||||
Fenofibrate | No Intervention | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/15 (0%) | 0/8 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Fenofibrate | No Intervention | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/15 (13.3%) | 0/8 (0%) | ||
Gastrointestinal disorders | ||||
Gastrointestinal discomfort | 2/15 (13.3%) | 2 | 0/8 (0%) | 0 |
Hepatobiliary disorders | ||||
Elevated liver enzymes | 2/15 (13.3%) | 2 | 0/8 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Michael F. La Fountaine, EdD, ATC, FACSM |
---|---|
Organization | James J. Peters VA Medical Center |
Phone | 718-584-9000 ext 3121 |
michael.lafountaine@va.gov |
- B1925-P